Toxicities of Pelvic Organs after High-Dose, Spot Scanning Based Proton Therapy for Sacral Neoplasms

Reporter: J. Taylor Whaley, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 21, 2012

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Presenter: Ralf Alexander Schneider
Presenter's Institution: Paul Scherrer Institute, Switzerland

Background

  • Mesenchymal tumors are tumors originating in tissues that develop into bone, cartilage, and muscle. Although rare as a whole, three of the more common types of mesenchymal tumors include chordomas, chondosarcomas, and sarcomas.
  • Chordomas are rare, slow-growing, tumors that have low metastatic potential, but are locally aggressive. They are thought to arise from embryonic remnants of primitive notochordal elements.
  • Sarcomas are a group of rare tumors that frequently originate from muscle, fat, and tendons and encompass a group of 50 different types of tumors.
  • Chordomas frequently occur in the sacrococcygeal region and approximately 10-20% of sarcomas are found in the trunk. With tumors in close proximity to numerous critical structures, including the spinal cord, bowel, bladder, and kidneys, treatment can be challenging with complete resection often impossible.
  • Although complete resection with or without radiation is the primary treatment, tumor location can often limit the feasibility of surgery. Due to the tendency for incomplete resection, radiation is frequently employed as neoadjuvant or adjuvant therapy. Furthermore, because of their large size and locally aggressive nature, these tumors frequently require high dose radiation for local control.
  • Due to dose limitations for the nearby critical spinal cord as well as other structures, dose escalation is difficult with photon radiation. Previous publications have demonstrated improved outcomes with surgery and conventional radiation greater than 60 Gy for sarcomas. With conventional photon-based radiation therapy, doses capable of rendering local control have been difficult, if not impossible, to attain without unacceptable toxicity.
  • Owing to the high risk of long-term complications following high dose radiation to the pelvis, attempts to minimize normal tissue exposure to radiation are highly desired. Dosimetric comparisons of proton radiation have suggested an improvement in dose to normal tissues relative with photon-based radiotherapy, secondary to the steep dose fall off beyond the Bragg peak. It is thought that this improvement in dosimetric parameters will potentially mitigate toxicity.
  • The purpose of this study was to correlate target coverage and dose-volume histograms of pelvic organs at risk with clinical tolerance to proton radiation.

Methods

  • From September 1997 to August 2011, 25 patients with mesenchymal tumors were treated at the Paul Scherrer Institute Center for Proton Therapy.
  • Mean age was 55.1 years (Range, 30-81 years), with 11 females and 14 males.
  • Diagnosis was chordoma in 76%, sarcoma in 12%, and chondrosarcoma in 12%.
  • Six patients have complete resections, 7 patients had gross total resections, 9 patients had partial resections, and 3 patients had biopsy only.
  • Proton therapy with spot-scanning was prescribed to a mean total dose of 72.3 GyE (range, 56-77.4 Gy) delivered in 1.8 to 2 Gy per fraction. Direct posterior or posterior oblique fields were utilized.
  • 23/25 patients received at least 68 Gy.
  • 24/25 patients were treated prone. All patients were treated with individualized vacuum mold for immobilization.
  • No patients received chemotherapy.
  • Follow up period ranged from 0.3 to 10.9 years (Mean, 3.9 yrs). Eighty percent had a minimum follow up of 2 years.
  • Based on planning CT, dose distributions to the organs at risk, including rectum, bladder, ovaries, vagina, uterus, and penile bulb were analyzed.
  • Retrospective review of these 25 patients was reviewed and clinical outcomes with rates of disease control are presented.

Results

  • Mean high-dose target volume was 1403 cc (Range, 73-7149 cc).
  • 94% of the high dose volumes were covered by 90% prescribed dose, and 89.5% of the high dose volumes were covered by 95% prescribed dose.
  • 3-year actuarial local control rate was 54% (13/24) and 3-year actuarial overall survival was 70% (17/24).
  • At the time of analysis, 7 patients have died. Five patients died of disease with 4 patients progressing locally. Two patients had unrelated deaths.
  • Despite target doses greater than 70 GyE, rectal volume received >50/ >60/ >70 GyE in only 60%/ 32%/ 4%, respectively.
  • Mean max dose to the bladder was 36 Gy.
  • Only 5 patients received mean dose to the ovaries greater than 2.5 Gy.
  • Two patients developed Grade 1 acute bowel toxicity. 48% of patients developed Grade 2 radiation dermatitis, and 20% of patients developed grade 3 radiation dermatitis.
  • One patient developed avascular bone necrosis.
  • Three patients (12%) developed Grade 2 chronic skin reaction.
  • Three patients (12%) experienced Grade 2 neuropathies of peripheral nerves.
  • No patients experienced greater than Grade 2 acute or late adverse events were observed.

Authors' conclusions

  • For patients with large sacral tumors, proton therapy offers an excellent tool when target volumes require doses of radiation greater than 70 Gy. Proton therapy offers a viable option for dose escalation as normal tissues can be largely avoided.
  • In the authors' small retrospective study, there was nearly a complete absence of pelvic toxicity with the bladder, ovaries, vagina, uterus, and penile bulb not limiting target dose.
  • Further follow up is required to evaluate the delayed side effects of proton therapy.

Clinical/Scientific Implications

  • Mesenchymal tumors, consisting of chordomas, chondosarcomas, and sarcomas, within the pelvis offer clinicians challenging cases, as high dose radiation (>70 Gy) is needed to control tumors.
  • The authors present their experience with spot scanning based proton radiotherapy for mesenchymal tumors of the pelvis and evaluate the toxicity associated with high dose therapy. The presentation is certainly a valuable contribution to the standing body of literature.
  • The dosimetric advantages of proton therapy are apparent with dramatic improvements for pelvic organs at risk, and the acute toxicity appears to be acceptable.
  • These tumors represent rare tumors with aggressive natural histories. Due to the small number of cases diagnosed annually, randomized and prospective trials are difficult to perform. The majority of literature involves retrospective reports from single institutions.
  • Information on late effects and long term outcomes associated with this treatment remains will certainly contribute to the literature when longer follow-up permits analysis of quality of life and disease control following proton beam radiotherapy.


News
ASTRO: Combination Therapy Beneficial in Prostate Cancer

Aug 22, 2014 - Long-term survival may be increased in medium-risk prostate cancer patients who receive short-term androgen deprivation therapy before and during radiation treatment compared with men who receive radiation alone. In addition, proton beam therapy may be associated with a decreased risk of disease recurrence after 10 years and has minimal side effects after one year, according to research presented at the 51st Annual Meeting of the American Society for Radiation Oncology, held from Nov. 1 to 5 in Chicago.



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